5-nitro-2-furaldehyde-2-ethyl semicarbazone blackhead control compositions and method of using same



- ITRO-2-FURALDEHYDE 2 ETHYL SEMICAR- BAZONE BLACKHEAD CONTRQL COMPOSI-TIONS AND METHOD OF USING SAME Cornell Alvin Johnson, Norwich, N.Y.,assignor to The Norwich Pharmacal Company, a corporation of New York NoDrawing. Filed Sept. 4, 1962, Ser. No. 221,325

2 Claims. (Cl. 167-53.1)

This invention relates to veterinary medicine and is concerned withnovel compositions adapted for the control of histomoniasis, which issometimes referred to as infectious enterohepatitis and most commonlycalled blackhead, which term will be used herein, in Aves. Moreparticularly this invention is concerned with novel compositionscontaining 5-nitro-2-furaldehyde 2 ethyl semica rbazone useful for theprevention and control of blackhead in poultry, especially in turkeys.

Black-head is a frequently encountered disease of poultry causing severeeconomic loss to the grower unless its appearance in the poultry flockis diligently watched for and its progress promptly counteracted whenobserved. Precise husbandry to curtail this disease poses insurmountableobstacles in practice necessitating resort to agents effective in itsalleviation to impart confidence to the raiser that appropriatemanagement coupled 'with therapy will prevent ravage of the flock.

In the turkey, blackhead is caused by the protozoan Histomonasmeleagridis, which affects the ceca and liver, by the ingestion thereofor of the cecal worm Heterakis gallinae which provides a haven for thatprotozoan. Prognosis of the disease is poor. Mortality occurs in highpercentage. When the birds do not sucumb to the disease, they are soinferior in quality that they are substantially an economic loss.

I have discovered that 5-nitro-2-furaildehyde-2-ethyl semicarbazone uponoral administration in relatively low and substantially non-toxicamounts to turkeys evinces a surprisingly effective therapy in thecontrol of blaekhead. In the practice of my invention I have found thatcombining 5-nit-ro-2-furaldehyde-Z-ethyl semicarbazone With the feedsupply is an easy and convenient method for its administration. Thiscombination is readily effected by admixing the active ingredients,5-nitro-2-furaldehyde-2- ethyl semicarbazone, with commonly usedelements of poultry sustenance such as grains, soybean meal, fish meal,vitaminaceous sources, alfalfa meal, mineral components and mixturesthereof by grinding, stirring or tumbling in apparatus conventionallyused for that purpose. The p-reparation of 5-nitro-2-furaldehyde-2-ethylsemicarbazone is fully disclosed in Journal of Organic Chemistry, vol.14, page 813, 1949.

The amount of active ingredient required to provoke an effectivetherapeutic management of blackhead is within the range of about 0.0085%to about 0.022% by weight of the ultimate composition in which it isoffered. It is apparent that lesser amounts of active agent will sutfieeUnited States Patent 0 when compositions containing it are providedprophylactically and greater amounts are indicated when fulminating,acute infections are encountered.

Illustrative of the beneficial results aiforded by the oraladministration of 5-nitro-2-furaldehyde-2-ethyl semicarbazone to turkeysexposed to and infected by Histomonas meleagridis, in accordance with myinvention, are the following examples:

EXAMPLE I Prophylactic test One hundred-thirty two straight run, broadbreasted White Holland turkey poults, twenty-three days of age, wereWing banded, weight balanced, and were distributed into three groups offorty-four birds. They were then placed in floor pens measuring 11' x 9with a total area of 99 sq. ft. Adequate space was available to thepoults for the first six weeks of the study since each turkey poult fromone to nine weeks old requires a minimum of one square foot of floor penspace for maximum growth and development. Each floor pen was equippedwith a hang-- Group I5-nit-ro-2-furaldehyde 2 ethyl semicarbazone GroupII-Inoculated controln'o medication.

Group IIINon-inocula ted controlno medication.

The poults were weighed individually at weekly intervals and all poultswhich died were autopsied and the livers and ceca examined for evidenceof blackhead infection.

Thirty-seven days after inoculation, at which time the poults were nineweeks old, all groups were weighed and reduced in number to twentypoults in order that each remaining poult would have the minimum of foursquare feet of floor pen space required for optimal growth anddevelopment to market age. The poults selected for elimination comprisedboth the lightest and the heaviest poults in .a group, and those closestto the mean weight were retained.

The remaining twenty poults were maintained for an additional forty-twodays. During this time weekly Weight gains were again recorded.

Feed consumption records were kept throughout the entire period ofseventy-nine days in order that feed conversion values could becalculated. The results are depicted in the following table:

Mortality Periodic Mean Weights o1 Poults 1n Grams Total Feed GroupAverage Conver- Gatn sions D/t Percent 5/12 5/15 1 5/23 5/31 6/6 I 6/136/21 2 6/28 7/12 7/15 7/19 7/26 8/2 3/44 6. 8 258. 0 319.0 635. 8 918.Oil, 216. 5 1, 562. 9 1, 882. 8 2, 436. 8 2, 960. 9 3, 475. 9 3, 943.04,301.0 4, 562. 2 4, 294. 2 2.92 19/44 43. 2 268. 0 307.0 610. 6 751. 21, 063.3 1, 575. 6 1, 920. 3 2,378.3 2, 861. 5 3, 374. 6 3, 748. 84,033.1 4, 487. 8 4, 219. 8 3. 34 0/44 271. 0 325. 4 610.9 983. 7 1,300. 1 1, 646. 2 2, 094.0 2, 472. 2 3, 081.0 3, 734. 8 4, 042.8 4, 551.2 4, 953. 4 4, 682. 4 2. 62

1 Day of inoculation and start of medication. 2 All groups were reducedto twenty poults.

3 EXAMPLE n Prophylaiic test One hundred and twenty straight run, broadbreasted White Holland turkey poults, two weeks old, were individuallyweighed, wing banded and weight balanced into six groups of equalnumbers. Three groups were assigned at random to replicate number one,and the three remaining groups were assigned to replicate number two.Each replicate, which was maintained in a separate battery in the samecubicle, contained one group medicated withS-nitro-Z-furaldehyde-Z-ethyl semicarbazone and two groups maintainedwithout medication which served as inoculated and non-inoculatedcontrols. Medication was incorporated into standard turkey starter mashwhich was supplied ad libitum for thirteen weeks.

When approximately five weeks old, each of the experimental poults andthose maintained for inoculated contr ols were orally administered 150embryonated Hefera'kis poults were individually weighed and wing handed,and two groups were then inoculated inter-rectally with 1 ml. volumes ofa virulent culture of Histomonas meleagridis. Each dose containedapproximately 4 10- viable histomonads. Six days later, one inoculatedgroup was placed on continuous medication which consisted of 5-nitro-Z-furaldehyde 2 ethyl semicarbazone (0.0165%) (Group I) instandard turkey starter mash. The second inoculated group (Group II)which served as the inoculated, non-medicated control and the remainingnoninoculated group (Group III) which was used for weight gaincomparisons were continued on standardturkey starter mash ad libitum.The poults were individually weighed at weekly intervals and all poultsthat died during the course of the study were autopsied and examined forgross blackhead pathology. At the termination of the four week floor pentest weekly average percentlweight gains and total average percentweight gains were calculated. The results are depicted in the followinggallinae ova suspended in one ml. volumes of 0.75% can table:

Mortality Periodic Mean Weights in Grams and Per- Total Days oi .cent;Gains Percent Group Infection Gain Medicated 6/30-7/28 D/t Percent 6/307/6 1 7/14 7/21 7/28 19. 1% 11. 4% 14. 6% 9. 1 65. 9% II 6-28 9/15 60. 02, 259. a 2, 653. 3 2,263. 9 2, 360. 2 2, 937. 5

17. 4% 14. 7% 4. 3% 24. 5% 30. 0% III 0/15 0 2, 522. 6 2, 893. 3 3, 333.7 3, 713. 9 3, 959. 1

1 Start oi medication.

What is claimed is:

1. A composition for the control of blackhead in poultry comprising incombination a poultry feed and from about 0.0085 to about 0.022% byweight thereof of 5- nitro-2-furaldehyde-Z-ethyl semicarbazone.

2. A process for combatting blackhead in poultry which comprises orallyadministering thereto an element of poultry sustenance havingdistributed therein 5-nitro-2- furaldehyde-Z-ethyl semicarbazone.

Periodic Average Weights and Average Gains in Grams Av. Percent gain atFeed or- Group age 15 efiitality Initial Final weeks eiency due to Wt.12/12 12/20 12/27 1 1/3 1/10 1/17 1/24 1/31 2/7 2/14 Wt. black- 12/5 3/6head anemone no. 1

5-nitro-2-iuraldehyde-2-ethyl semicarbazone (0.011%) 140. 9 311. 9 548.6 822. 2 1, 194. 1 1, 443. 5 1, 841. 1 2, 281. 0 2, 701. 1 3, 092.6 3,608. 9 5, 075.0 4, 934. 1 3. 15 5 171. 0 236. 7 273. 6 371. 249. 397.439. 9 420. 391. 5 516. 3 1, 466. 0 Inoculated Control 141.1 301. 4 512.6 764. 6 1, 079. 1 1, 234. 5 1, 416.0 1, 896.6 2,305.0 2, 668. 3 3, 175.8 4, 756. 6 4, 615. 5 3. 49

4 160.3 211. 2 252.0 314. 155. 181. 480. 6 408. 363. 3 507. 5 1, 580. 8Non-inoculated Control 141. 1 304.0 533. 2 780. 9 1, 124. 4 1, 364. 3 1,728.0 2, 194.5 2, 569. 7 2, 964. 5 3, 461. 5 4, 875. 1 4, 734. 0 3. 41 0162. 9 229. 2 247. 7 343. 5 239. 363. 466 5 5. 2 394. 8 497. 1, 413.6BEPLICATE N0. 2

5-11itro-2-furaldehyde-2-ethyl semicarbazone (0.011%) 141. 0 305. 7 532.3 775.0 1, 099. 8 1, 315.3 1, 654. 0 2, 041. 1 2, 424. 7 2, 801. 1 3,279. 4 4, 686.1 4, 545.1 3. 40 5 164. 7 226. 6 242. 7 324. 8 215. 5 338.7 387. 383. 6 376. 4 478. 3 1, 406. 7 Inoculated ControL 141. 0 302. 5513.6 788. 5 1, 134. 2 1, 203.0 1, 413.0 1, 842.0 2, 250. 0 2, 628.0 3,072.0 4, 414.0 4, 273. 0 3. 52

' 161. 5 211. 1 274. 9 345. 7 68.8 210. 429. 408. 0 378. 0 444. 0 1,342.0 Non-inoculated Control 141. 0 297. 5 526. 7 756. 5 1, 102. 8 1,349. 5 1, 678. 0 2, 123. 0 2, 549. 5 2, 958. 0 3, 391. 5 4, 723. 7 4,582. 7 3. 46 0 1 Poults were two weeks old when placed on medication (20birds per group). 2 Poults were inoculated by gavage with approximatelyembryonated Heterakts gallinae ova. 8 Poults were moved from cages tofloor pens two days after January 3, 1962 weighing.

EXAMPLE III References Cited by the Examiner Delayed medication testUNITED STATES PATENTS Forty-five ten week old, straight run,broad-breasted 70 2,416,234 1947 St lman 260-345 White Holland turkeyswere randomly divided into three groups of fiteen poults and were placedin 4% x 5 /2 floor pens with hanging feeders and metal waterers. All

JULIAN s. LEVITT, Primary Examiner.

FRANK CACCIAPAGLIA, JR., Examiner.

2. A PROCESS FOR COMBATTING BLACKHEAD IN POULTRY WHICH COMPRISES ORALLYADMINISTERING THERETO AN ELEMENT OF POULTRY SUSTENANCE HAVINGDISTRIBUTED THEREIN 5-NITRO-2FURALDEHYDE-2-ETHYL SEMICARBAZONE.